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Hepatitis C: Identification Of A Protein That Inhibits The Virus

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Scientists in the Laboratoire Hépatite C of the Institut de Biologie de Lille in collaboration with INSERM Unit 602 and a laboratory at Stanford University have provided evidence of a protein, called EWI-2wint, that inhibits the hepatitis C virus at an early stage of its infective cycle. This research suggests possible new perspectives for the development of therapies to block the virus before it enters a cell.
The EWI-2wint protein is not present in hepatocytes (liver cells). When it comes into contact with the hepatocyte, the hepatitis C virus can thus bind to the CD81 protein, which will allow it to enter the cell and pursue its infective cycle. In other types of cells in the body, the EWI-2wint protein is present and interacts with CD81, thus preventing the hepatitis C virus from entering these cells. (Credit: Copyright CNRS 2008 Sophana Ung)

Hepatitis C is a major public health problem that affects some 130 million people throughout the world. In France , where there are about 5000 new cases each year, it is estimated that half a million people could be affected by this disease. The causal agent is the hepatitis C virus (HCV) which targets cells in the liver called hepatocytes. HCV infection is usually chronic (60% to 80% of cases) and in the long term can lead to the development of cirrhosis and liver cancer.

Unlike the hepatitis A and B viruses, there is no vaccine to combat this virus. Furthermore, the treatments employed are only of limited efficacy (the failure rate reaches around 40%), and they involve considerable side effects. It is therefore crucial to develop new antiviral compounds to control this infection.

HCV uses at least three receptors to enter and infect a hepatocyte. One of these receptors is the CD81 protein, which has the particular characteristic of associating with numerous other proteins. It was by studying these CD81 partner proteins that the researchers identified the EWI-2wint protein, which prevents the recognition of CD81 by the hepatitis C virus and inhibits it at a very early stage in its infective cycle. This protein is present in other types of cells, which could explain why they are not infected by HCV. Discovery of the role of EWI-2wint in hepatocytes has demonstrated the complexity of the mechanisms of entry of HCV into its target cells, and opens the way to new therapeutic approaches.

PLoS ONE. 2008 Apr 2;3(4):e1866.
The CD81 partner EWI-2wint inhibits hepatitis C virus entry.

Institut de Biologie de Lille (UMR8161), CNRS, Universités de Lille I et Lille II, Institut Pasteur de Lille, Lille, France.

Two to three percent of the world’s population is chronically infected with hepatitis C virus (HCV) and thus at risk of developing liver cancer. Although precise mechanisms regulating HCV entry into hepatic cells are still unknown, several cell surface proteins have been identified as entry factors for this virus. Among these molecules, the tetraspanin CD81 is essential for HCV entry. Here, we have identified a partner of CD81, EWI-2wint, which is expressed in several cell lines but not in hepatocytes. Ectopic expression of EWI-2wint in a hepatoma cell line susceptible to HCV infection blocked viral entry by inhibiting the interaction between the HCV envelope glycoproteins and CD81. This finding suggests that, in addition to the presence of specific entry factors in the hepatocytes, the lack of a specific inhibitor can contribute to the hepatotropism of HCV. This is the first example of a pathogen gaining entry into host cells that lack a specific inhibitory factor.

Written by huehueteotl

April 17, 2008 at 8:45 am

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